Metallothionein expression and nuclear size in benign, borderline, and malignant serous ovarian tumours

Metallothioneins (MTs) are low‐molecular‐weight proteins involved in metalloregulatory functions such as cell proliferation, growth, and differentiation. In recent years, MT expression has been linked with carcinogenesis, resistance to cancer therapy, and tumour progression. However, the significance of MT expression in ovarian cancers is at present inadequately documented. In this study, MT immunohistochemistry was performed in 12 benign, 14 borderline, and eight malignant serous tumours of the ovary. The intensity of the immunostaining was evaluated by image analysis. There was a significantly higher number of MT‐immunopositive cells in the multilayered epithelial cells of borderline serous tumours (atypical proliferative serous tumours) than in the single layered epithelial cells within the same tumour, and in the single cell layer of benign serous tumours. There was no difference in the expression of MTs in the single layered tumour cells of benign and borderline serous tumours. Significantly higher numbers of MT‐immunopositive cells were observed in both the single and the multilayered epithelial cells of serous carcinomas, the highest number being observed in the multiple layers of serous carcinomas. The positively stained malignant tumour cells in both single and multiple layers were larger than the negatively stained cells in benign, borderline, and malignant serous ovarian tumours. There was moderate to intense staining. These findings indicate that there is increased expression of MTs in the progression of malignancy, which could be used as a marker in grading the three groups of ovarian serous tumours and for determining prognosis. Copyright © 1999 John Wiley & Sons, Ltd.

[1]  M. Renan,et al.  Increased radioresistance of tumor cells exposed to metallothionein-inducing agents. , 1989, Radiation research.

[2]  R. Scully,et al.  Symposium: ovarian tumors of borderline malignancy. , 1996, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[3]  K. Rizkalla,et al.  Metallothionein: A potential marker for differentiating benign and neoplastic gastrointestinal lymphoid infiltrates , 1997, Pathology.

[4]  M. Karin Metallothioneins: Proteins in search of function , 1985, Cell.

[5]  K. Schmid,et al.  Significance of metallothionein overexpression in human tumours , 1997, Histopathology.

[6]  B. Jasani,et al.  Immunohistochemical detection of metallothionein. , 1991, Methods in enzymology.

[7]  B. Jasani,et al.  Age‐related changes in metallothionein, copper, copper‐associated protein, and lipofuscin in human liver: A histochemical and immunohistochemical study , 1990, The Journal of pathology.

[8]  R. Foster,et al.  Cell-type specific and differential regulation of the human metallothionein genes. Correlation with DNA methylation and chromatin structure. , 1990, The Journal of biological chemistry.

[9]  R. Ozols,et al.  Mechanisms of drug resistance in ovarian cancer , 2010, Cancer.

[10]  H. Goulding,et al.  Metallothionein expression in human breast cancer. , 1995, British Journal of Cancer.

[11]  W. Dinjens,et al.  EXPRESSION OF NUCLEOPHOSMIN/B23 IN NORMAL AND NEOPLASTIC COLORECTAL MUCOSA , 1996, The Journal of pathology.

[12]  T. Bauknecht,et al.  Gene structure and expression analysis of the epidermal growth factor receptor, transforming growth factor‐alpha, myc, jun, and metallothionein in human ovarian carcinomas classification of malignant phenotypes , 1993, Cancer.

[13]  I. Bremner,et al.  Nutritional and physiological significance of metallothionein. , 1987, Experientia. Supplementum.

[14]  J. Lazo,et al.  Metallothionein null cells have increased sensitivity to anticancer drugs. , 1995, Cancer research.

[15]  J. Lazo,et al.  Role of metallothionein in carcinogenesis. , 1994, Toxicology and applied pharmacology.

[16]  Paul J Thornalley,et al.  Possible role for metallothionein in protection against radiation-induced oxidative stress. Kinetics and mechanism of its reaction with superoxide and hydroxyl radicals. , 1985, Biochimica et biophysica acta.

[17]  J. Kägi Overview of metallothionein. , 1991, Methods in enzymology.

[18]  B. Bay,et al.  Interphase and M-phase oral KB carcinoma cells are targetted in staurosporine-induced apoptosis. , 1996, Cancer letters.

[19]  D. Hamer,et al.  Cell specificity and an effect of ras on human metallothionein gene expression. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[20]  J. Brisson,et al.  Markers of chemoresistance in ovarian carcinomas: an immunohistochemical study of 86 cases. , 1996, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[21]  J. Chin,et al.  Immunohistochemical localization of metallothionein in transitional cell carcinoma of the bladder. , 1991, The Journal of urology.

[22]  B E Miller,et al.  The prognostic value of image analysis in ovarian cancer , 1991, Cancer.

[23]  E. Goncharova,et al.  A role for metallothionein and zinc in spontaneous mutagenesis. , 1994, Cancer research.

[24]  A. Monks,et al.  Metallothionein gene expression and resistance to cisplatin in human ovarian cancer , 1990, International journal of cancer.

[25]  D Komitowski,et al.  Quantitative nuclear morphology in the diagnosis of ovarian tumors of low malignant potential (borderline) , 1989, Cancer.